Phomopsis seed decay (PSD) is an economically important seed disease in soybean, Glycine max (L.) Merrill. This disease is primarily caused by a seed-borne fungus, Phomopsis longicolla T. W. Hobbs (syn. Diaporthe longicolla). Information about the pathogenic mechanism of the fungus is lacking. The objectives of this study were to analyze protein-protein interactions (PPI) and to identify conserved global networks and pathogenicity subnetworks in P. longicolla, which include orthologous pathways for cell signaling and pathogenesis. Genome-wide analysis of the predicted protein interactome with the interlog method revealed 215,255 unique PPIs among 3,868 proteins. A total of 1,414 pathogenicity related genes in P. longicolla were also identified using the pathogen host interaction database. In addition, 149 plant cell wall degrading enzymes (PCWDE) were detected. The most predominant class of PCWDE was a group of 60 glycoside hydrolase proteins. The glycoside hydrolase subnetwork was found to be interacting with 1,442 proteins. The orthologous proteins FUS3, HOG, CYP1, SGE1, and the g5566t.1 gene identified in this study could play an important role in pathogenicity. The P. longicolla protein interactome generated in this study can enhance our knowledge about PPIs in soybean pathogens and aid in developing new strategies for disease control.